Method for demonstrating presence or absence of markers associated with the presence and/or the chemosensitivity of tumors

This is a §371 of International Application No. PCT/EP2006/068943, with an international filing date of Nov. 27, 2006 (WO 2007/060240 A2, published May 31, 2007), which is based on French Patent Application Nos. 05/11954, filed Nov. 25, 2005, and 05/11958, filed Nov. 25, 2005.

This disclosure relates novel methods with which to evidence the presence of absence of markers associated with tumors and their sensitivity to chemotherapies. The disclosure also relates diagnostic kits comprising means enabling the methods to be implemented, and relates the use of compounds inhibiting the activity or expression of the markers to inhibit the growth of tumor cells.

In the area of pathologies, cancers occupy a predominant position in terms of prevalence, incidence and mortality. Cancer-forming phenomena are related to complex cell disorders, not well known, which may affect all the organs. The means for screening and fighting cancers remain imperfect.

There is a large variety of tumor phenomena which may occur at any age of an individual and affect most functional areas of a human body. In particular, the central nervous system (CNS), a complex organ consisting of numerous different cell types, is no exception to these morbid and most diversified pathological phenomena. Indeed there are numerous types of solid brain tumors. These tumors correspond to the development of oncological phenomena affecting the constituent cells of the CNS (neuronal cells, glial cells.). Also there exist other localized tumors in the CNS which are the result of metastases derived from tumors of other organs. CNS tumors are characterized by a certain number of anatomical, biological and clinical parameters. At the current time, careful analysis of these parameters predominantly determines the strategy of therapeutic action taken by the clinician. The specific phenotype of a tumor is an element which, still most imperfectly, allows the prognostic evaluation of a patient\'s chances of survival.

Amongst the investigations which can be used to classify brain tumors, mention may be made of:

• • medical imaging (tomodensitometry and magnetic resonance imaging)
  • morphological and histological analysis performed on biopsies
  • biomolecular analysis: search for protein markers by immune-detection, cytogenetic analysis (e.g., detection of genetic macro-anomalies by probe hybridization).

The diagnosis of tumors and more particularly of CNS tumors is predominantly based on histological analysis conducted by an anatomo-pathologist. Unfortunately diagnostic discrepancies observed between experts in the area are enormous (up to 64% disagreement depending on tumors). Worse still, similar discrepancies can be noted when the interpretations of identical samples are given to the same person at a few weeks\' interval (Mittler et al, 1996; Bruner et al, 1997; Coons et al, 1997). This finding is worrying since it is known that diagnosis errors may lead to unnecessary radiotherapy and/or chemotherapy with heavy consequences for the patient.

As a supplement to histological analysis, there are only a few rare diagnosis tests based on molecular approaches. Cytological observations for example can be completed by the search for genetic anomalies and, in some laboratories, by the detection of certain protein markers using specific antibodies.

At the present time no routine tests exist based on the detection and quantification of the concentration of transcriptomic tumor markers. The few molecular tests currently available do not allow a non-ambiguous differentiation to be made between the different types of tumor cells, and especially do not allow correct prognosis of their sensitivity to cytotoxics with accuracy.